Ahmed F. Abdel-Magid & Stéphane Caron 
Fundamentals of Early Clinical Drug Development 
From Synthesis Design to Formulation

An informative look at the intricacies of today’s drug development
process

Once a discovery organization has identified a potential new drug
candidate, it is the daunting task of synthetic organic chemists to
identify the chemical process suitable for preparation of this
compound in a highly regulated environment. Only through a
multi-layered chemical process that takes into account such factors
as safety, environmental considerations, freedom to operate and
cost-effectiveness can researchers begin to refine the drug in
terms of quality and yield.

This book covers both recent advances in the design and synthesis
of new drugs, as well as the myriad other issues facing a new drug
candidate as it moves through the development process. Utilizing
recent case studies, the authors provide valuable insights into the
complexities of the process, from designing new synthetic
methodologies and applying new automated techniques for finding
optimal reaction conditions to selecting the final drug form and
formulation.

Both novice and active researchers will appreciate the inclusion of
chapters on such diverse topics as:

* Cross-coupling methods

* Asymmetric synthesis

* Automation

* Chemical Engineering

* Application of radioisotopes

* Final form selection

* Formulations

* Intellectual property

A wealth of real-world examples and contributions from leading
process scientists, engineers, and related professionals make this
book a valuable addition to the scientific literature.

Table of Content

Contributors.

Preface.

1. Reflections on Process Research II (Edward J. J.
Grabowski).

2. Development and Scale-Up of a Heterocyclic Cross-Coupling for
the Synthesis of
5-[2-(3-Methyl-3H-imidazol-4-yl)-thieno[3, 2-b]pyridine-7-yl]
amino-2-methyl-1H-indole (John A. Ragan).

3. Large-Scale Enantioselective Preparation of 2E, 7E,
5S, 6R, 5-Hydroxy-6-methyl-8-phenyl-octa-2, 7-dienoic Acid, a Key
Fragment for the Formal Total Synthesis of the Anti-tumor Agent
Cryptophycin 52 (James Aikins, Tony Y. Zhang, Milton Zmijewski,
and Barbara Briggs).

4. Efforts Toward a Commercially Viable Route and Process to the
Synthesis of HIV PI GW640385X (John C. Roberts, Roman Davis,
Brian D. Doan, Thomas C. Lovelace, Daniel E. Patterson, Frank
Roschangar, Barry Sickles, Jennifer F. Toczko, and Ju
Yang).

5. Development of an Asymmetric Synthesis of ABT-100 (Albert
W. Kruger, Michael J. Rozema, Bridget D. Rohde, Bhadra Shelat,
Lakshmi Bhagavatula, James J. Tien, Weijiang Zhang, and Rodger F.
Henry)

6. Asymmetric Hydrogenation: A New Route to Pregabalin (Rex
Jennings, William S. Kissel, Tung V. Le, Edward Lenoir, Thomas
Mulhern, and Robert Wade).

7. Responsibilities of the Process Chemist: Beyond Synthetic
Organic Chemistry (Stéphane Caron).

8. Outsourcing–The Challenge of Science, Speed, and
Quality (Simone Andler-Burzlaff, Jason Bertola, and Roger E.
Marti).

9. Automation and the Changing Face of Process Research in the
Pharmaceutical Industry (Edward J. Delaney, Merrill L. Davies,
Brent D. Karcher, Victor W. Rosso, A. Erik Rubin, and John J.
Venit)

10. Large-Scale Synthesis: An Engineering Perspective (Joseph
H. Childers, Jr.)

11. Synthesis and Application of Radioisotopes in Pharmaceutical
Research and Development (Larry E. Weaner and David C.
Hoerr).

12. Selection of the Drug Form in Exploratory Development
(George J. Quallich).

13. Strategies to Achieve Particle Size of Active Pharmaceutical
Ingredients (David J. am Ende and Peter R. Rose).

14. Challenges in Early Formulation: Turning Drug Substance into
Drug Product (Mark H. Kleinman and Beeah Lee).

15. Intellectual Property and Early Development (Maria I.
Shchuka).

Index.

About the author

AHMED F. ABDEL-MAGID is a Senior Research Fellow in Chemical
and Pharmaceutical Development at Johnson & Johnson
Pharmaceutical Research & Development, L.L.C.

STÉPHANE CARON is a Director in Chemical Research
and Development at Pfizer Global R&D.